Rafal Dziadziuszko1, Tony Mok2, Solange Peters3, Ji-Youn Han4, Jorge Alatorre-Alexander5, Natasha Leighl6, Virote Sriuranpong7, Maurice Pérol8, Gilberto de Castro Junior9, Ernest Nadal10, Filippo de Marinis11, Osvaldo Arén Frontera12, Daniel S W Tan13, Dae Ho Lee14, Hye Ryun Kim15, Mark Yan16, Todd Riehl17, Erica Schleifman17, Sarah M Paul17, Simonetta Mocci17, Rajesh Patel17, Zoe June Assaf17, David S Shames17, Michael S Mathisen17, Shirish M Gadgeel18. 1. Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. 2. State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong. 3. Oncology Department, University Hospital (CHUV), University of Lausanne, Switzerland. 4. Center for Lung Cancer, National Cancer Center, Goyang, South Korea. 5. Thoracic Oncology Clinic, Health Pharma Professional Research, Mexico City, Mexico. 6. Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 7. Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 8. Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France. 9. Division of Clinical Oncology, Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil. 10. Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain. 11. European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy. 12. Centro de Investigación Clínica Bradford Hill, Santiago, Chile. 13. Division of Medical Oncology, National Cancer Centre Singapore, Singapore. 14. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 15. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, South Korea. 16. F. Hoffmann-La Roche, Mississauga, Canada. 17. Genentech, Inc., South San Francisco, California. 18. Department of Internal Medicine, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan. Electronic address: sgadgee1@hfhs.org.
Abstract
INTRODUCTION: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. METHODS: Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response. RESULTS: In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6-18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5-93.5) by investigator and 92.0% (95% CI: 84.1-96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6-88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9-98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1-87.7). Safety data were consistent with the known tolerability profile of alectinib. CONCLUSIONS: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.
INTRODUCTION: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. METHODS: Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response. RESULTS: In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6-18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5-93.5) by investigator and 92.0% (95% CI: 84.1-96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6-88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9-98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1-87.7). Safety data were consistent with the known tolerability profile of alectinib. CONCLUSIONS: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.
Authors: Johannes Noé; Walter Bordogna; Venice Archer; Vlatka Smoljanovic; Magalie Hilton; Ryan Woodhouse; Simonetta Mocci; Shirish M Gadgeel Journal: JTO Clin Res Rep Date: 2022-05-18